title: IB-367 pre-treatment improves the in vivo efficacy of teicoplanin and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus.
abstract: Antimicrobial peptides are known as immunomodulators and antibiotic enhancers. We report that administration of an antimicrobial peptide, IB-367, was efficacious in increasing the antimicrobial activity of daptomycin and teicoplanin in a mouse model of wound infection caused by meticillin-resistant Staphylococcus aureus (MRSA). Mice were assigned to seven groups: an IB-367 pre-treated group with no antibiotics given after challenge, two IB-367 pre-treated groups plus daptomycin or teicoplanin given after challenge, two groups treated with daptomycin or teicoplanin only after challenge, and two control groups without infection or that did not receive any treatment. The main outcome measures were quantitative bacterial culture and analysis of natural killer (NK) cytotoxicity and leukocyte phenotype. The wound, established through the panniculus carnosus muscle of mice, was infected by MRSA. Bacterial cultures of mice receiving antibiotics alone showed a -2 log decrease, whilst those for IB-367 plus daptomycin or teicoplanin showed a -4 log decrease. IB-367 plus daptomycin showed the highest efficacy. The higher antimicrobial effect exerted by IB-367 was associated with increased levels of NK cytotoxicity but not of NK cell number. IB-367 increased the number of both CD11b and Gr-1 cells 3 days after MRSA challenge, whereas both of these leukocyte populations were reduced at 10 days after challenge. Our data suggest that a combination of IB-367 with antibiotic exerts a therapeutic effect and may be useful for the management of staphylococcal wounds.
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Oscar
authors.initials: O
authors.lastname: Cirioni
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Silvestri
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA - IRRCS, Ancona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Pierpaoli
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA - IRRCS, Ancona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Barucca
authors.affiliation: Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kamysz
authors.affiliation: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ghiselli
authors.affiliation: Department of Plastic and Reconstructive Surgery General Surgery, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scalise
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Brescini
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Castelli
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA - IRRCS, Ancona, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kamysz
authors.affiliation: General Surgery and Surgery Methodology Clinic, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Guerrieri
authors.affiliation: Institute of Infectious Diseases and Public Health, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giacometti
authors.affiliation: Experimental Animal Models for Aging Unit, Scientific Technological Area, INRCA - IRRCS, Ancona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Provinciali
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D058491:Bacterial Load; D017576:Daptomycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification*; D051379:Mice; D008807:Mice, Inbred BALB C; D013203:Staphylococcal Infections / Q000188:drug therapy*; D017334:Teicoplanin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014946:Wound Infection / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D023181:Antimicrobial Cationic Peptides; D017334:Teicoplanin; D017576:Daptomycin; C119872:antimicrobial peptide IB-367